This invention generally pertains to heterocyclic carbon compounds having drug and bio-affecting properties and to their preparation and use. In particular, the invention is concerned with 4-(1-naphthyl)-piperidines and tetrahydropyridines with substituted aryl or hetarylaminoalkyl moieties attached at the N-1 position of the monazine. These compounds inhibit the reuptake of serotonin and potently bind at 5-HT.sub.1A, 5-HT.sub.1D and 5-HT.sub.2 receptor sites. This pharmacology renders the compounds useful in treating depression. In addition, these compounds have reduced dopaminergic and .alpha.-adrenergic binding activities compared to diazine analogs such as piperazines.
Simple naphthylalkylamines and naphthylpiperazines have been reported to bind at 5-HT.sub.1D receptor sites. (See: Glennon, et al., Drug Development Research, 22:25-36 (1991).)
Chenard, et al., WO 94 121619 disclosed a series of 1,7-disubstituted naphthalene derivatives (1) claimed to have, inter alia, antidepressant action. The central heterocyclic ring in (1) was ##STR2## piperazine, dihydropyridine or piperidine while R.sup.3 was hydrogen, alkyl, alkoxyalkyl, aryl or arylalkyl.
The most relevant art appears to be a series of U.S. patents to Lavielle, et al., that disclose and claim an extensive series of 5-HT.sub.1A agonists (2) that are disclosed as being useful in treating a variety of disorders including depression. ##STR3##
Lavielle, et al., discloses naphthylpiperidine (U.S. Pat. No. 5,250,544); naphthyl tetrahydropyridine (U.S. Pat. No. 5,292,711); and naphthyl piperazine (U.S. Pat. No. 5,166,156) analogs of (2), wherein B is an amido, sulfonamido, imido or phthalimido moiety. Also disclosed as synthetic intermediates are compounds wherein B is --CN and --NH.sub.2.
Of less interest are the series of compounds of Tran, et al., WO 94 02473, wherein piperazine amides (3) were disclosed as having, inter alia, antidepressant properties. ##STR4##
In (3), A is either --NHCO-- or --CONH--.
Similarly, Perrone, et al., WO 94 00441 disclose piperazine derivatives (4) having antidepressant action among other biological activities. ##STR5##
A in (4) is either --NH(CH.sub.2)n-- or --(CH.sub.2)n--.
The foregoing references do not teach nor suggest the specific combination of structural variations leading to the novel secondary and tertiary aminoalkyl derivatives of 4-(1-naphthyl)-tetrahydropyridines and piperidines which not only possess specific 5-HT binding properties but also inhibit 5-HT reuptake. The added advantage of reduced dopaminergic and .alpha.-adrenergic activities make the instant compounds superior antidepressant agents.